Academic literature on the topic 'Biochemistry and Cell Biology N.E.C'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Biochemistry and Cell Biology N.E.C.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Biochemistry and Cell Biology N.E.C"
1
Van Langevelde, Arjen, Kees Van Malssen, René Driessen, Kees Goubitz, Frank Hollander, René Peschar, Peter Zwart, and Henk Schenk. "Structure of C n C n+2C n -type (n = even) β′-triacylglycerols." Acta Crystallographica Section B Structural Science 56, no. 6 (December 1, 2000): 1103–11. http://dx.doi.org/10.1107/s0108768100009927.
Full textAbstract:
The crystal structures of the β′ phase of CLC (1,3-didecanoyl-2-dodecanoylglycerol) and MPM (1,3-ditetradecanoyl-2-hexadecanoylglycerol) have been determined from single-crystal X-ray diffraction and high-resolution X-ray powder diffraction data, respectively. Both these crystals are orthorhombic with space group Iba2 and Z = 8. The unit-cell parameters of β′-CLC are a = 57.368 (6), b = 22.783 (2) and c = 5.6945 (6) Å and the final R value is 0.175. The unit-cell parameters of β′-MPM are a = 76.21 (4), b = 22.63 (1) and c = 5.673 (2) Å and the final Rp value is 0.057. Both the β′-CLC and β′-MPM molecules are crystallized in a chair conformation, having a bend at the glycerol moiety. The zigzag planes of the acyl chains are orthogonally packed, as is typical for a β′ phase. Furthermore, unit-cell parameters of some other members of the C n C n+2C n -type triacylglycerol series have been refined on their high-resolution X-ray powder diffraction pattern. Finally, the crystal structures are compared with the currently known structures and models of triacylglycerols.
2
Yang, Ruojing, and James M. Trevillyan. "c-Jun N-terminal kinase pathways in diabetes." International Journal of Biochemistry & Cell Biology 40, no. 12 (January 2008): 2702–6. http://dx.doi.org/10.1016/j.biocel.2008.06.012.
Full text
3
Barth, Holger, Klaus Aktories, Michel R. Popoff, and Bradley G. Stiles. "Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins." Microbiology and Molecular Biology Reviews 68, no. 3 (September 1, 2004): 373–402. http://dx.doi.org/10.1128/mmbr.68.3.373-402.2004.
Full textAbstract:
SUMMARY Certain pathogenic species of Bacillus and Clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic “A-B” paradigm for protein toxins. The binary toxins produced by B. anthracis, B. cereus, C. botulinum, C. difficile, C. perfringens, and C. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. The “B” components are synthesized as precursors that are subsequently activated by serine-type proteases on the targeted cell surface and/or in solution. Following release of a 20-kDa N-terminal peptide, the activated “B” components form homoheptameric rings that subsequently dock with an “A” component(s) on the cell surface. By following an acidified endosomal route and translocation into the cytosol, “A” molecules disable a cell (and host organism) via disruption of the actin cytoskeleton, increasing intracellular levels of cyclic AMP, or inactivation of signaling pathways linked to mitogen-activated protein kinase kinases. Recently, B. anthracis has gleaned much notoriety as a biowarfare/bioterrorism agent, and of primary interest has been the edema and lethal toxins, their role in anthrax, as well as the development of efficacious vaccines and therapeutics targeting these virulence factors and ultimately B. anthracis. This review comprehensively surveys the literature and discusses the similarities, as well as distinct differences, between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine. The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria.
4
FORMICKA-KOZLOWSKA, Grazyna, Helga SCHNEIDER-BERNLOHR, Jean-Pierre WARTBURG, and Michael ZEPPEZAUER. "H8Zn(c)2 and Zn(c)2Co(n)2 human liver alcohol dehydrogenase." European Journal of Biochemistry 173, no. 2 (April 1988): 281–85. http://dx.doi.org/10.1111/j.1432-1033.1988.tb13996.x.
Full text
5
Krapp, Anne, Vera Saliba-Colombani, and Françoise Daniel-Vedele. "Analysis of C and N metabolisms and of C/N interactions using quantitative genetics." Photosynthesis Research 83, no. 2 (February 2005): 251–63. http://dx.doi.org/10.1007/s11120-004-3196-7.
Full text
6
May, Gerhard H. W., K. Elizabeth Allen, William Clark, Martin Funk, and David A. F. Gillespie. "Analysis of the Interaction between c-Jun and c-Jun N-terminal Kinasein Vivo." Journal of Biological Chemistry 273, no. 50 (December 11, 1998): 33429–35. http://dx.doi.org/10.1074/jbc.273.50.33429.
Full text
7
Yeap, Yvonne Y. C., Ivan H. W. Ng, Bahareh Badrian, Tuong-Vi Nguyen, Yan Y. Yip, Amardeep S. Dhillon, Steven E. Mutsaers, John Silke, Marie A. Bogoyevitch, and Dominic C. H. Ng. "c-Jun N-terminal kinase/c-Jun inhibits fibroblast proliferation by negatively regulating the levels of stathmin/oncoprotein 18." Biochemical Journal 430, no. 2 (August 13, 2010): 345–54. http://dx.doi.org/10.1042/bj20100425.
Full textAbstract:
The JNKs (c-Jun N-terminal kinases) are stress-activated serine/threonine kinases that can regulate both cell death and cell proliferation. We have developed a cell system to control JNK re-expression at physiological levels in JNK1/2-null MEFs (murine embryonic fibroblasts). JNK re-expression restored basal and stress-activated phosphorylation of the c-Jun transcription factor and attenuated cellular proliferation with increased cells in G1/S-phase of the cell cycle. To explore JNK actions to regulate cell proliferation, we evaluated a role for the cytosolic protein, STMN (stathmin)/Op18 (oncoprotein 18). STMN, up-regulated in a range of cancer types, plays a crucial role in the control of cell division through its regulation of microtubule dynamics of the mitotic spindle. In JNK1/2-null or c-Jun-null MEFs or cells treated with c-Jun siRNA (small interfering RNA), STMN levels were significantly increased. Furthermore, a requirement for JNK/cJun signalling was demonstrated by expression of wild-type c-Jun, but not a phosphorylation-defective c-Jun mutant, being sufficient to down-regulate STMN. Critically, shRNA (small hairpin RNA)-directed STMN down-regulation in JNK1/2-null MEFs attenuated proliferation. Thus JNK/c-Jun regulation of STMN levels provides a novel pathway in regulation of cell proliferation with important implications for understanding the actions of JNK as a physiological regulator of the cell cycle and tumour suppressor protein.
8
Mooney, Lorraine M., and Alan J. Whitmarsh. "Docking Interactions in the c-Jun N-terminal Kinase Pathway." Journal of Biological Chemistry 279, no. 12 (December 29, 2003): 11843–52. http://dx.doi.org/10.1074/jbc.m311841200.
Full text
9
Cain, Stuart A., Andrew K. Baldwin, Yashithra Mahalingam, Bertrand Raynal, Thomas A. Jowitt, C. Adrian Shuttleworth, John R. Couchman, and Cay M. Kielty. "Heparan Sulfate Regulates Fibrillin-1 N- and C-terminal Interactions." Journal of Biological Chemistry 283, no. 40 (July 31, 2008): 27017–27. http://dx.doi.org/10.1074/jbc.m803373200.
Full text
10
Bagowski, Christoph P., Wen Xiong, and James E. Ferrell. "c-Jun N-terminal Kinase Activation inXenopus laevisEggs and Embryos." Journal of Biological Chemistry 276, no. 2 (October 11, 2000): 1459–65. http://dx.doi.org/10.1074/jbc.m008050200.
Full textDissertations / Theses on the topic "Biochemistry and Cell Biology N.E.C"
1
Buchanan, Fritz G. "Endogenous Alkylglycerol Functions As a Mediator of Protein Kinase C Activity and Cell Proliferation." Digital Commons @ East Tennessee State University, 1997. https://dc.etsu.edu/etd/2885.
Full textAbstract:
To explore the possibility that 1-O-alkyl-sn-glycerol (alkylglycerol) may serve a regulatory role in the control of cell proliferation or PKC activity, we examined the ability of alkylglycerol to influence PKC activity and subcellular distribution as well as the ability of alkylglycerol to effect cell proliferation. MDCK cells grown to confluence show a loss of PKC activity associated with the membrane, as reported in fibroblasts. Preconfluent cultures of MDCK cells have a high level of PKC activity associated with the membrane. However, treatment of preconfluent cultures with alkylglycerol causes a reduction of PKC activity. A similar inhibition was observed with alkylglycerol when cells were treated with TPA, an activator of PKC. To confirm that alkylglycerol was exerting an effect directly on PKC, alkylglycerol was shown to inhibit PKC activity in vitro in a dose dependent manner. Since PKC exists as a family of closely related isozymes, we have determined the effects of growth arrest and alkylglycerol treatment on PKC $\rm\alpha,\ \epsilon,\ and\ \zeta$ (expressed in MDCK cells). The active forms of PKC $\alpha$ and $\epsilon$ are lost early in the growth of MDCK cells during the endogenous accumulation of alkylglycerol and synthetic alkylglycerol inhibits the membrane form of PKC $\alpha$ and $\epsilon.$ However, alkylglycerol inhibits the TPA induced translocation of PKC $\alpha$ but not $\epsilon$ suggesting a differential inhibition among these isoforms. Neither TPA or alkylglycerol had any effects on the distribution of PKC $\zeta.$ To examine the effect of alkylglycerol on cell proliferation, Swiss 3T3 cells were used. GLC analysis shows that 3T3 cells accumulate alkylglycerol in a similar manner as MDCK cells. Since this accumulation occurs just prior to cell growth arrest, the effects of alkylglycerol on preconfluent cells was observed. Preconfluent cultures of 3T3 cells were treated with alkylglycerol on day 1 of growth. After 8 days of culture, the treated group showed a slower growth rate and saturation density. Furthermore, after these cells were reseeded in the absence of alkylglycerol, the original growth rate and saturation density returned. Thus alkylglycerol induces a decrease in cell proliferation without causing any detrimental effects. Similarly, alkylglycerol was found to inhibit the induction of mitogenesis by TPA (a PKC dependent pathway) and these effects were shown not to be stereospecific. To further investigate the effect of alkylglycerol on cell proliferation, the content of the monoglycerides in ras-transformed cells was analyzed. These cells have lost contact dependent growth arrest indicating a disruption of cell growth regulation. We observed a massive increase in the content of alkylglycerol during the culture of ras transformed cells. This increase is 3 fold higher than MDCK or 3T3 cells. This raises the possibility that alkylglycerol may be the end result of an increased number of cell-cell contacts. We have observed an increase in the accumulation of alkylglycerol in normal and ras-transformed cells. This accumulation is accompanied by a decrease in PKC activity and alkylglycerol was shown to be a potent in vitro inhibitor of PKC. Similarly, alkylglycerol was shown to inhibit PKC $\alpha$ under stimulation by TPA. Alkylgylcerol is a inhibitor of the TPA induced induction of mitogenesis and slows the growth rate of proliferating cultures of 3T3 cells. These results indicate that the endogenous ether-linked glycerolipid, alkylglycerol, is a regulator of cell proliferation through its inhibitory effects on protein kinase C. (Abstract shortened by UMI.)
2
Williams, Kendra Allana. "Phosphorylation of Histone Deacetylase 6 within its C-terminal Region by Extracellular Signal Regulated Kinase 1." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4792.
Full text
3
Gu, Cong. "Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3887.
Full textAbstract:
Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and initiates the human innate immune response or serve as a direct entry route for productive infection of pathogen. Dictyostelium discoideum, soil-living amoeba, a unicellular eukaryote that could professionally internalize fluid phase or particles several folds more than that of macrophages and neutrophils. Additionally, multiple key signaling pathways are conserved between Dictyostelium and mammalian cells, including pathways affecting small GTPases Ras and Rac and their downstream effectors, and F-Actin remodeling. All these traits makes Dictyostelium an excellent model organism to study the process pf macropinocytosis and phagocytosis.
Upon internalization of the prey, these macropinocytes and phagocytes are often in an environment of increased production of superoxide radicals in the prey-containing vesicles, which helps stimulates the downstream signaling pathways to digest the prey inside. However, the mechanism of how superoxide regulates the process of macropinocytosis and phagocytosis is not fully understood. We had previously reported that Dictyostelium cells lacking Superoxide dismutase C (SodC) exhibited aberrantly high level of active RasG, high basal level of Phosphatidylinositol-3,4,5-triphosphate (PIP3), and severe chemotaxis defects. Now we report that sodC- cells displayed aberrant endosomal vesicle trafficking, significantly compromised particle uptake and defective cell to substratum matrix adhesion compared to that of wild type cells. By using high resolution live imaging microscope we also show that sodC- cells have defects in F-Actin remodeling at the phagocytic rim extension and F-Actin depolymerization of the nascent phagosome. Interestingly, the introduction of overexpressing of cytoplasmic superoxide dismutase (SodA), redox insensitive RasG (C118A) or treatment of PI3K inhibitor LY294002 in sodC- cells significantly rescued the defects of endosomal vesicle trafficking, particle uptake and adhesion. This project suggests that superoxide dismutase C regulates the endosomal vesicle trafficking, phagocytosis and cell to substratum matrix adhesion through the RasG/PI3K signaling axis in Dictyostelium cells.
4
Unsworth, Amanda J. "The role of protein kinase C in platelet activation." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:114582b8-185a-41f5-958c-77038fb185df.
Full textAbstract:
The Protein kinase C (PKC) superfamily is a key regulator in platelet activation with individual isoforms playing distinct roles. This thesis focuses on the role of the novel PKC isoforms downstream of several agonists using both pharmacological and genetic approaches and human and mouse platelets. Quantification of the protein levels of PKC isoforms identified different levels of the five major PKC isoforms expressed in human platelets and also differences between levels of the same isoform in human and mouse platelets. Use of a selection of broad spectrum and isoform-specific inhibitors, identified both positive and negative novel roles for PKC in the regulation of human and mouse platelets. A net positive role for PKC was found in GPVI, Clec-2, and PAR receptor signalling, with classical isoforms of PKC playing a major role in aggregation and dense granule secretion. A novel negative regulatory role was also identified in the regulation of ADP-induced platelet activation for PKC~, and both PKCE and PKC~ in human and mouse platelets respectively. Gene knock-out mouse models confirmed a positive regulatory role for PKCe in allb~3 outside-in signalling but identified no other regulatory role for PKCe in agonist induced platelet activation. Despite this relatively minor role, functional redundancy was identified between PKCe and PKCE isoforms in haemostasis, as tail bleeding was significantly increased in mice deficient in both novel isoforms. The work presented here identifies key roles for the PKC superfamily in the complex regulation of platelet activation, with different isoforms supporting and limiting the process of thrombus formation and haemostasis.
5
Hiyama, Jun. "Isolation and characterisation of N-glycans of ovine and human luteinizing hormones." Thesis, University of Auckland, 1991. http://hdl.handle.net/2292/1989.
Full textAbstract:
Gonadotrophic hormones are heterodimeric glycoproteins and their N-glycans attached to specific amino acid residues are currently thought to play important roles in hormonal biosynthesis, secretion and function. The studies reported in this thesis aimed at isolation and characterisation of structural properties of the N-glycans on ovine and human luteinizing hormones. Initially, chromatographic methods were developed using reverse-phase HPLC for the analytical separation of the three human pituitary glycoprotein hormones and their subunits. Separation of intact oLH and its subunits was also effected by a single HPLC step. A preparative procedure was developed for the efficient purification of hLH and hTSH from crude human pituitary extracts using hydrophobic chromatography which gave highly purified hormones in good yields and with high biological activities. This method did not significantly influence the hormones' extensive charge heterogeneity and it offered potential advantages in the characterisation of their carbohydrate structures. A preparative scheme was developed for the isolation of the N-linked oligosaccharides from each glycosylation site of o- and hLH. Charge heterogeneity of oligosaccharides, which were released by hydrazinolysis from subunits and glycopeptides, was characterised by anion-exchange HPLC. 1H-NMR analysis showed that the structures of all three N-glycans on hLH were highly heterogeneous but mainly diantennary complex-type, with site-specific patterns of terminal sialylation and sulphation as well as core-fucosylation. Sulphated/sialylated and/or disialylated oligosaccharides were the major components at each site. A set of new mono- and disialylated oligosaccharides with the terminal sequence NeuAcα2-6GalNAcβ1-4G1-cNAcβ1-2Manα1-3 was identified. This finding suggested unique site-specific terminal sialylation of oligosaccharides at Asn 78 (hLHα) by an unknown α2-6 sialyltransferase(s) in the human pituitary gonadotroph cell. Each glycosylation site in oLH had a distinct set of oligosaccharides ranging from mainly monosulphated hybrid-type at the two sites of oLHα to predominantly disulphated diantennary complex-type on oLHβ. Core-fucosylation also differed at each site. These results suggested that processing of the oligosaccharides of the α- and β-subunits by α-mannosidase II and α1-6 fucosyltransferase was differently regulated by protein structure in oLH. Whereas hCG, hLH and oLH share similar biological activities, no apparent relationship between their N-glycan structures was found, which suggested that specific branching and peripheral structures of N-glycans on LH and hCG may not be essential for biological function, although the N-glycan nearer the N-terminus of the α-subunit of hCG has been implicated in hormonal activity.
6
Lumngwena, Evelyn Ngwa. "The impact of HIV-1 subtype C Envelope N-glycosylation on DC-SIGN meditated modulation of DC function to facilitate transmission or enhance viral pathogenesis." Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/27096.
Full textAbstract:
N-glycosylation plays an important role in Envelope (Env) function and may be involved in the modulation of the immune response to HIV-1 infection. In this study, we hypothesized that Env N-glycosylation may affect viral pathogenesis by influencing Env structure and function. Furthermore, we also postulated that differences in Env glycosylation could affect interactions between Env and DC-SIGN of dendritic cells (DCs), activating alternative signalling pathways which stimulate the release of different immune modulators. We generated pseudovirus of eighteen Env clones (PSVs) with variable number and position of potential N-glycan sites (PNGs) and compared their ability to infect TZM-bl cells, bind to Raji+ DC-SIGN cells, trans-infect TZM-bl cells when captured by either Raji-DC-SIGN cells or monocyte-derived dendritic cells (MDDCs) and modulate MDDC signaling by investigating the release of Interleukin-10 (IL-10) and other immune modulatory cytokines and MAPK activation. Entry efficiency, DC-SIGN binding and trans-infection varied widely across all clones. The level of IL-10 secreted by MDDCs in response to PSV stimulation varied 32-fold. The induction of IL-10 secretion by purified gp140 confirmed that Env was the viral component that stimulated the secretion of IL-10 via interaction with DC-SIGN and potentially other undefined receptors. PSV and purified gp140 stimulated MDDC signaling via ERK and JNK phosphorylation, while p38 was not activated. The addition of recombinant DC-SIGN lowered the levels of secreted IL-10 and ERK /JNK phosphorylation, suggesting that DC-SIGN plays a role in these responses. As Env mannosylation correlated with DC-SIGN binding, five highly conserved Env PNGs (241, 262, 386, 392, and 448) previously identified to carry high mannose type N-glycans and hence thought to be involved in DC-SIGN binding were deleted in two Env clones by site-directed mutagenesis to confirm their importance in Env function. The potential role of these PNGs in Env entry efficiency, DC-SIGN binding, trans-infection, induction of MDDC IL-10 secretion and activation of MAPK phosphorylation was determined. Deletion of these sites significantly affected the entry efficiency, DC-SIGN binding, trans-infection and MDDC IL-10 secretion, with one Env clone proving to be more sensitive to mutation than the other. This suggests that PNGs influence Env function in a clone-specific manner. As deletion of highly conserved PNGs abrogated Env function we used sequence analysis to identify PNGs involved in binding DC-SIGN and inducing MDDC IL-10 secretion. We grouped PSVs based on the presence or absence of specific PNGs in Env sequences and compared entry efficiency, DC-SIGN binding, trans-infection, stimulation of MDDC IL-10 secretion and induction of MAPK phosphorylation. Three Env PNGs were significantly associated with entry efficiency (N356, N392, and N674), and three sites (N289, N356 and 674) were significantly associated with trans-infection while N674 also influenced DCSIGN binding. The majority of MDDC donors secreted higher levels of IL-10 when stimulated with PSVs that carried PNGS at N130 (p = 0.0016) and N332 (p = 0.0039) and lacked N674 (p = 0.033). When Envs were graded on whether they had 0, 1, 2 or 3 of the PNGs (e.g. -130, -332, +674; -130, +332 and +674, etc.) those that carried either one of the PNGs or the entire induction motif (N130+ N332+ N674-) significantly stimulated MDDCs to secrete higher levels of IL-10 than those that completely lacked the motif (p = 0.0335 and p = 0.0304, respectively). As the presence of N674 was linked to reduction in all functions of Env, it is likely that the presence of an N-glycan at this site affected Env structure and could skew the analysis. Excluding N674 indicated that the presence of PNGs at position 130 and 332 was sufficient to induce significantly higher IL-10 release than those that had either none or one of these sites (p = 0.0053). When we determined whether N130 and N332 were enriched in subtype C acute infection Envs, these sequences were not enriched with PNGs at either N130 or N332 compared to chronic infection viruses. However, when IL-10 levels were compared between MDDC donors stimulated with PSV of either acute or chronic infection clones, those from early infection significantly enhanced MDDC secretion of IL-10 (p = 0.0039). This suggests that even though PNGs at 130 and N332 could be involved in inducing MDDC IL-10 secretion, it is not the only requirement for enhanced stimulation. Although Env differentially activated ERK and JNK phosphorylation, ERK phosphorylation did not correlate with IL-10 secretion, suggesting that this MAPK signaling pathway was not solely responsible for triggering the release of MDDC IL-10 and other regulatory cytokines. PSVs also stimulated the release of TNFα, IL-1β, IL-6, IL-8, MIP-1a, and MIP-1b while having no effect on IL-12 levels. This suggests that HIV-1 binding to DCs in the genital tract could change the dynamics of DC immune responses, deregulating their cytokines secretion and destabilising the Th0 cell differentiation to facilitate viral survival and thus productive clinical infection. We therefore conclude that HIV-1 variants differentially stimulate MDDCs to release immunosuppressive IL-10 and that transmitted founders could be better at modulating immune responses in the genital tract compared to chronic infection variants.
7
Dagälv, Anders. "Role of Heparan Sulfate N-sulfation in Mouse Embryonic Development." Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-123474.
Full textAbstract:
Heparan sulfate (HS) is a sulfated glycosaminoglycan expressed by all cells in the body. It is found at the cell surface and in the extracellular matrix where it binds a large amount of various ligands including growth factors and morphogens. HS is important for building up morphogen gradients during embryonic development and to act as coreceptors for signaling molecules. Many different Golgi enzymes are involved in the biosynthesis of HS. It is known that some of these enzymes interact with each other but not how the whole biosynthesis machinery works or how the cell regulates the structure of the HS that it produces. In this thesis, cells and mice deficient in two of these biosynthetic enzymes, glucosaminyl N-deacetylase/N-sulfotransferase-1 (NDST1) and the isoform NDST2 have been studied. NDSTs perform the first modifications during biosynthesis where they replace N-acetyl groups on N-acetyl-glucosamine units with sulfate groups. It is known that deficiency of NDST1 is lethal, while lack of NDST2 only results in abnormal connective tissue type mast cells. Here it is shown that deficiency of both NDST1 and NDST2 is embryonically lethal. The embryonic stem (ES) cells extracted from the inner cell mass of double knockout blastocysts show in addition an impaired differentiation capacity compared to wild-type ES cells and fail completely to differentiate into cardiac muscle cells which NDST1-/-, NDST2-/- and wild-type ES cells all do. Cultured mast cells that lack NDST2 produce heparin that is low-sulfated compared to wild-type HS. To our surprise, we could show that mast cells deficient in NDST1 instead produce a more highly sulfated heparin than wild-type cells. We use a model that predicts that the biosynthesis enzymes work together in a multienzyme complex, the GAGosome, to explain our results. We hypothesize that NDST1 has a higher affinity for the GAGosome than NDST2 which only in the absence of NDST1 gets incorporated into the enzyme complex. When all GAGosomes contain NDST2, a more highly sulfated glycosaminoglycan chain will be synthesized. A splice variant of NDST1, NDST1S, has also been studied. We could show that NDST1S lacks enzyme activity but that it probably has the capacity to incorporate into GAGosomes. Overexpression of NDST1S results in altered structure of the HS produced by the cells. We speculate that expression of the splice variant during development may be one way to regulate HS structure.
8
de, Jesus Tristan J. "Novel Mechanisms of Immune Regulation by NF-kappaB c-Rel." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1576176282590614.
Full text
9
Giblin, Sean. "Investigating cell lineage specific biosynthesis of tenascin-C during inflammation." Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:8c7306d8-53cf-4131-a134-f74885e37cc9.
Full textAbstract:
The extracellular matrix (ECM) is a complex network of molecules secreted by cells, which is essential for providing structural support and facilitating cell processes including adhesion, migration and survival. Tenascin-C is an immunomodulatory ECM protein that exhibits limited expression in healthy tissues, but is transiently elevated at sites of tissue injury, and is persistently expressed in chronic inflammatory diseases and tumours. Alternative splicing of 9 of tenascin-C's fibronectin type III-like domains (FnIII- A1, A2, A3, A4, B, AD2, AD1, C and D) generates enormous diversity in form; yielding 511 possible isoforms. Post-transcriptional modification of tenascin-C has been studied in cancer and during development where disease and tissue specific isoforms exhibit distinct adhesive, migratory and proliferative effects. However, little is known of how tenascin-C is expressed or alternatively spliced during inflammation. This study characterises inflammation and disease specific tenascin-C isoforms made by immune cells and fibroblasts, and investigates their functional relevance. Biosynthesis and alternative splicing of tenascin-C was examined using standard curve qPCR, ELISA, Western blot and confocal immunocytochemistry in resting and activated primary human immune cells, dermal fibroblasts, and in synovial fibroblasts isolated from healthy controls and from osteoarthritis (OA) and rheumatoid arthritis (RA) patients. Based on these data, three recombinant proteins comprising FnIII domains AD2-AD1, B-C-D and B-AD2-AD1-C-D were cloned, expressed and purified, and their impact on cell behaviour including adhesion, morphology and migration was assessed. Basal tenascin-C expression was lower in myeloid and lymphoid cells than fibroblasts, and was induced in all following inflammatory stimulation. Tenascin-C expression was elevated in disease with RA and OA synovial fibroblasts containing higher levels than healthy controls. Alternative splicing following cell activation was cell-type specific: all FnIII except AD2 and AD1 were upregulated in dendritic cells and macrophages, in T-cells all FnIII remained unchanged with FnIII A1 absent; and no change in splicing was observed in activated dermal fibroblasts. Normal and OA synovial fibroblasts exhibited similar tenascin-C splicing patterns, but FnIII B and D were specifically elevated in RA. Functional analysis revealed differences in the adhesion, morphology and migration of myeloid cells and dermal fibroblasts cultured on FnIII AD2-AD1, B-C-D, B-AD2-AD1-C-D and full length tenascin-C substrates; FnIII B-C-D promoted MDDC migration while B-AD2-AD1-C-D promoted fibroblast adhesion, compared to full length tenascin-C. For the first time, this study reveals differences in tenascin-C biosynthesis and alternative splicing by immune cells and fibroblasts following activation with inflammatory stimuli; and starts to reveal how alternative splicing of tenascin-C may influence the behaviours of both stromal and immune cells types during inflammation and in inflammatory diseases.
10
Smith, Abigail O. "Defining the Role of c-Jun N-terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1141.
Full textAbstract:
Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins Polycystin-1 (PKD1) and Polycystin-2 (PKD2). The most proximal effects of polycystin mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The stress-activated mitogen-activated protein kinase (MAPK) pathway c-Jun N-terminal kinase (JNK) promotes proliferation in specific contexts and is activated in acute and chronic kidney disease. Previous work found evidence of JNK activation in cystic tissues (Le et al., 2005) and others showed that JNK signaling is activated by aberrant expression of PKD1 and PKD2 in cell culture (Arnould et al., 1998; Arnould et al., 1999; Parnell et al., 2002; Yu et al., 2010) but the contribution of JNK signaling to cystic disease in vivo has not been investigated.
This body of work describes the use of conditional and germline deletion of Pkd2, Jnk1 and Jnk2 to model ADPKD and JNK signaling inhibition in juvenile and adult mice. Immunoblots and histological staining were used to measure JNK activation and evaluate the effect of JNK deletion on cystic disease. Results show that Pkd2 deletion activated JNK signaling in juvenile and adult mice. Reduction of JNK activity significantly reduced cystic burden in kidneys of juvenile Pkd2 mutant mice. This correlated with reduced tubule cell proliferation and reduced kidney fibrosis. The improvement in cystic phenotype was driven primarily by Jnk1 deletion rather than Jnk2. JNK signaling inhibition in adult Pkd2 mutants significantly reduced liver cysts when mice were aged six months. JNK inhibition reduces the severity of cystic disease caused by the loss of Pkd2 suggesting that the JNK pathway should be explored as a potential therapeutic target for ADPKD.
Books on the topic "Biochemistry and Cell Biology N.E.C"
1
R, Harris James, ed. Ascorbic acid: Biochemistry and biomedical cell biology. New York: Plenum Press, 1996.
Find full textBook chapters on the topic "Biochemistry and Cell Biology N.E.C"
1
"Refractive Index, n D 20 ° C of Alkyl Monoesters of Carboxylic and Diesters of Dicarboxylic Acids." In Handbook of Biochemistry and Molecular Biology, edited by Gerald D. Fasman, 493. CRC Press, 2019. http://dx.doi.org/10.1201/9780429487293-32.
Full text
2
Fields, Gregg B., and Janelle L. Lauer-Fields. "Principles and Practice of Solid-Phase Peptide Synthesis." In Synthetic Peptides. Oxford University Press, 2002. http://dx.doi.org/10.1093/oso/9780195132618.003.0006.
Full textAbstract:
Peptides play key structural and functional roles in biochemistry, pharmacology, and neurobiology, and are important probes for research in enzymology, immunology, and molecular biology. The amino acid building blocks can be among the 20 genetically encoded L-residues, or else unusual ones, and the sequences can be linear, cyclic, or branched. It follows that rapid, efficient, and reliable methodology for the chemical synthesis of these molecules is of utmost interest. A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the sweet dipeptide L-Asp-L-Phe-OMe (aspartame) to clinically used hormones such as oxytocin, adrenocorticotropic hormone, calcitonin, and gonadotropin releasing hormone (GnRH) super-agonists. Synthesis can lead to potent and selective new drugs by judicious substitutions that change functional groups and/or conformations of the parent peptide. These include introduction of N- or C-alkyl substituents, unnatural or D-amino acids, side-chain modifications including sulfate or phosphate groups or carbohydrate moieties, and constraints such as disulfide bridges between half-cystines or side-chain lactams between Lys and Asp or Glu. Commercially important products that evolved from such studies include protease inhibitors, such as captopril and other angiotensin converting enzyme (ACE) inhibitors, peptidomimetic HIV protease inhibitors, and the somatostatin analog lanreotide. Most of the biologically or medicinally important peptides which are the targets for useful structure-function studies by chemical synthesis comprise under 50 amino acid residues, but occasionally a synthetic approach can lead to important conclusions about small proteins (full or domains) in the 100-200 residue size range. Methods for synthesizing peptides are divided conveniently into two categories: solution (classical) and solid-phase pep tide synthesis (SPPS). The classical methods have evolved since the beginning of the twentieth century, and they are described amply in several reviews and books (Wünsch, 1974; Finn and Hofmann, 1976; Bodanszky and Bodanszky, 1984; Goodman et al, 2001). The solid-phase alternative was conceived and elaborated by R. B. Merrifield beginning in 1959, and has also been covered comprehensively (Erickson and Merrifield, 1976; Birr, 1978; Barany and Merrifield, 1979; Stewart and Young, 1984; Merrifield, 1986; Barany et al., 1987, 1988; Kent, 1988; Atherton and Sheppard, 1989; Fields and Noble, 1990; Barany and Albericio, 1991; Fields et al., 1992; Gutte, 1995; Fields, 1997; Lloyd-Williams et al., 1997; Chan and White, 2000; Kates and Albericio, 2000).
Conference papers on the topic "Biochemistry and Cell Biology N.E.C"
1
Schleuning, W. D. "THE BIOCHEMISTRY AND CELL BIOLOGY OF SINGLE CHAIN UROKINASE TYPE PLASMINOGEN ACTIVATOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642956.
Full textAbstract:
Urokinase was discovered in the late nineteenth century, as an enzymatic principle in urine, that initiates the dissolution of blood clots. The basis of this phenomenon was recognized more than fifty years ago as the activation of plasminogen, the precursor of a tryptic protease, then known as profibrinolysin. Despite this long history, detailed data on the biochemistry of plasminogen activation have only become available recently. Urokinase (now designated urokinase-type plasminogen activator : u-PA) is synthesized and secreted as a single chain polypeptide (Mr-: 53,000) by many cell types. Single chain u-PA (scu-PA) is with equal justification called prourokinase (pro-u-PA), notwithstanding its low catalytic activity for synthetic peptide substrates and plasminogen, as most proenzymes of proteases display a certain degree of activity. The structure of pro-u-PA has been elucidated by protein and cDNA sequencing. It consists of three domains, exhibiting characteristic homology to other proteins: a serine protease domain, homologous to trypsin, chymotrypsin and elastase; a kringle domain, likewise found in prothrombin, plasminogen, tissue-type plasminogen activator (t-PA) and Factor XII; and an epidermal growth factor (EGF)-like domain, found in many other proteins, including certain clotting factors. Pro-u-PA is activated by the cleavage of its LYS158-Ile159 h1 bY either plasmin or kallikrein. This cleavage leads to a high increase of Kcat values with respect to both plasminogen and synthetic peptide substrates, but apparently to a reduction of its affinity to plasminogen. Thrartoin inactivates pro-u-PA irreversibly by the cleavage of the Arg156-Phe157 bond. U-PA but not pro-u-PA rapidly forms ccnplexes with plasminogen activator inhibitors (PAI)-l and PAI-2: second order rate constants Kass are respectively > 107 and 0.9xl06 (M-11sec-1). Unknown enzymes process pro-u-PA and u-PA to low molecular weight (LMW) pro-u-PA and LMW u-PA (Mr: 33,000) by cutting off a fragment consisting of the kr ingle and the EGF—like region. Pro—u—PA mediated plasminogen activation is fibrin dependent in vivo, and to a certain degree in vitro. Hie biochemical basis of this fibrin specificity is at present uncertain, although there are reports indicating that it may require polyvalent cations. Through its EGF-like region HMW pro-u-PA and HMW u-PA are capable of binding to specific membrane protein receptors which are found on many cells. Thus, u-PA activity may be restricted to the cell surface. According to a recent report, binding of u—PA to the receptor may also mediate signal transduction in auto- or paracrine growth control. In cells permissive for the respective pathways, pro-u-PA gene transcription is stimulated by mechanisms of signal transduction, that include the cAMP, the tyrosine specific kinase and the protein kinase C dependent pathways. Glucocorticoid hormones downregulate pro-u-PA gene transcription in cells where the gene is canstitutively expressed. Although different cells vary greatly in their response to agents that stimulate urokinase biosynthesis, growth factors and other mitogens are in many cases effective inducers. Significantly elevated levels of u-PA are also found in many malignant tissues. These findings and many others suggest that plasminogen activation by u-PA provides localized extracellular matrix degradation which is required for invasive growth, cell migration and other forms of tissue remodelling. Fibrin represents in this view only a variant of an extracellular matrix, which is provided through the clotting system in the case of an emergency.